Shapira-Schweitzer Keren, Seliktar Dror
Faculty of Biomedical Engineering, Technion - Israel Institute of Technology, Technion City, Haifa 32000, Israel.
Acta Biomater. 2007 Jan;3(1):33-41. doi: 10.1016/j.actbio.2006.09.003. Epub 2006 Nov 13.
Successful implementation of cardiac cell transplantation for treating damaged myocardium relies on the development of improved injectable biomaterials. A novel biomaterial technology using PEGylated fibrinogen has been developed with controllable physicochemical properties based on the poly(ethylene glycol) (PEG) constituent. In addition, the fibrinogen backbone of the material confers inherent bioactivity to cells. The purpose of this investigation was to explore by in vitro techniques the use of this biomaterial as a scaffold for cardiac tissue regeneration. To this end neonatal rat cardiomyocytes were cultivated in PEGylated fibrinogen constructs. The cell-seeding density and biomaterial composition were optimized to obtain maximum spontaneous contraction of the constructs. Quantitative characterization of the contraction pattern was accomplished by video image analysis. It was possible to demonstrate an inverse correlation between the material stiffness and the amplitude of contraction of the tissue constructs by changing the modulus of the matrix using different compositions of PEG and fibrinogen. The relationship between matrix stiffness, cell density and tissue contraction also provided some insight into the mechanism of cellular remodeling that ultimately leads to synchronized contraction of the constructs. These findings indicate that PEGylated fibrinogen hydrogels can be used as a scaffold for cardiomyocytes, and offer the possibility of controlling cellular remodeling via simple compositional modifications to the matrix.
成功实施用于治疗受损心肌的心脏细胞移植依赖于改进的可注射生物材料的开发。一种基于聚乙二醇（PEG）成分、具有可控物理化学性质的新型生物材料技术——聚乙二醇化纤维蛋白原已被开发出来。此外，该材料的纤维蛋白原主链赋予细胞内在生物活性。本研究的目的是通过体外技术探索这种生物材料作为心脏组织再生支架的用途。为此，将新生大鼠心肌细胞培养在聚乙二醇化纤维蛋白原构建体中。优化细胞接种密度和生物材料组成以获得构建体的最大自发收缩。通过视频图像分析对收缩模式进行定量表征。通过使用不同组成的PEG和纤维蛋白原改变基质模量，有可能证明材料硬度与组织构建体收缩幅度之间呈负相关。基质硬度、细胞密度与组织收缩之间的关系也为最终导致构建体同步收缩的细胞重塑机制提供了一些见解。这些发现表明，聚乙二醇化纤维蛋白原水凝胶可作为心肌细胞的支架，并通过对基质进行简单的成分修饰提供控制细胞重塑的可能性。
